A Review of Repurposed Cancer Drugs in Clinical Trials for Potential Treatment of COVID-19.
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ABSTRACT:
SUBMITTER: Costa B
PROVIDER: S-EPMC8229933 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The COVID-19 pandemic caused by SARS-CoV-2 has placed severe constraints on healthcare systems around the globe. The SARS-CoV-2 virus has caused upheaval in the healthcare and economic sectors worldwide. On the 20th of May 2020, the World Health Organisation declared COVID-19 a global pandemic due to the unprecedented number of cases reported around the globe. As of the 4th of November 2022, there were 637,117,429 coronavirus cases reported globally by Worldometer stats, with 6,602,572 related deaths. In South Africa, there were approximately 4,029,496 coronavirus cases and 102,311 associated deaths. As such, there is a need for efficacious therapeutic regimes. There has been a paucity of knowledge encompassing the use of effective and specific antiviral drug therapies for treating COVID-19 since the outbreak. In this review, we provide valuable insights into the repurposing of current drugs for COVID-19. Drug repurposing provides a suitable option for the discovery of efficacious drugs for COVID-19, thereby decreasing the costs and turnaround times of drug development strategies. This review provides an overview of ten drugs, including antimalarial, antiparasitic, anti-inflammatory, nucleoside analogue, monoclonal-antibody drugs, that were repurposed for the potential treatment of COVID-19.
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Project description:Lung cancer patients are at heightened risk for developing COVID-19 infection as well as complications due to multiple risk factors such as underlying malignancy, anti-cancer treatment induced immunosuppression, additional comorbidities and history of smoking. Recent literatures have reported a significant proportion of lung cancer patients coinfected with COVID-19. Chloroquine, hydroxychloroquine, lopinavir/ritonavir, ribavirin, oseltamivir, remdesivir, favipiravir, and umifenovir represent the major repurposed drugs used as potential experimental agents for COVID-19 whereas azithromycin, dexamethasone, tocilizumab, sarilumab, famotidine and ceftriaxone are some of the supporting agents that are under investigation for COVID-19 management. The rationale of this review is to identify potential drug-drug interactions (DDIs) occurring in lung cancer patients receiving lung cancer medications and repurposed COVID-19 drugs using Micromedex and additional literatures. This review has identified several potential DDIs that could occur with the concomitant treatments of COVID-19 repurposed drugs and lung cancer medications. This information may be utilized by the healthcare professionals for screening and identifying potential DDIs with adverse outcomes, based on their severity and documentation levels and consequently design prophylactic and management strategies for their prevention. Identification, reporting and management of DDIs and dissemination of related information should be a major consideration in the delivery of lung cancer care during this ongoing COVID-19 pandemic for better patient outcomes and updating guidelines for safer prescribing practices in this coinfected condition.
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Project description:By January of 2023, the COVID-19 pandemic had led to a reported total of 6,700,883 deaths and 662,631,114 cases worldwide. To date, there have been no effective therapies or standardized treatment schemes for this disease; therefore, the search for effective prophylactic and therapeutic strategies is a primary goal that must be addressed. This review aims to provide an analysis of the most efficient and promising therapies and drugs for the prevention and treatment of severe COVID-19, comparing their degree of success, scope, and limitations, with the aim of providing support to health professionals in choosing the best pharmacological approach. An investigation of the most promising and effective treatments against COVID-19 that are currently available was carried out by employing search terms including "Convalescent plasma therapy in COVID-19" or "Viral polymerase inhibitors" and "COVID-19" in the Clinicaltrials.gov and PubMed databases. From the current perspective and with the information available from the various clinical trials assessing the efficacy of different therapeutic options, we conclude that it is necessary to standardize certain variables-such as the viral clearance time, biomarkers associated with severity, hospital stay, requirement of invasive mechanical ventilation, and mortality rate-in order to facilitate verification of the efficacy of such treatments and to better assess the repeatability of the most effective and promising results.
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Project description:The outbreak of Coronavirus disease 2019 (COVID-19) has evolved into an emergent global pandemic. Many drugs without established efficacy are being used to treat COVID-19 patients either as an offlabel/compassionate use or as a clinical trial. Although drug repurposing is an attractive approach with reduced time and cost, there is a need to make predictions on success before the start of therapy. For the optimum use of these repurposed drugs, many factors should be considered such as drug-gene or dug-drug interactions, drug toxicity, and patient co-morbidity. There is limited data on the pharmacogenomics of these agents and this may constitute an obstacle for successful COVID-19 therapy. This article reviewed the available human genome interactions with some promising repurposed drugs for COVID-19 management. These drugs include chloroquine (CQ), hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir (LPV/r), atazanavir (ATV), favipiravir (FVP), nevirapine (NVP), efavirenz (EFV), oseltamivir, remdesivir, anakinra, tocilizumab (TCZ), eculizumab, heme oxygenase 1 (HO-1) regulators, renin-angiotensin-aldosterone system (RAAS) inhibitors, ivermectin, and nitazoxanide. Drug-gene variant pairs that may alter the therapeutic outcomes in COVID-19 patients are presented. The major drug variant pairs that associated with variations in clinical efficacy include CQ/HCQ (CYP2C8, CYP2D6, ACE2, and HO-1); azithromycin (ABCB1); LPV/r (SLCO1B1, ABCB1, ABCC2 and CYP3A); NVP (ABCC10); oseltamivir (CES1 and ABCB1); remdesivir (CYP2C8, CYP2D6, CYP3A4, and OATP1B1); anakinra (IL-1a); and TCZ (IL6R and FCGR3A). The major drug variant pairs that associated with variations in adverse effects include CQ/HCQ (G6PD; hemolysis and ABCA4; retinopathy), ATV (MDR1 and UGT1A1*28; hyperbilirubinemia; and APOA5; dyslipidemia), NVP (HLA-DRB1*01, HLA-B*3505 and CYP2B6; skin rash and MDR1; hepatotoxicity), and EFV (CYP2B6; depression and suicidal tendencies).
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Project description:The uncertainty related to prevention and treatment of Coronavirus disease 2019 due to lack of effective vaccine candidates or drug molecules has resulted in extensive spread of infection and mortality worldwide. Although the asymptomatic or mild patients are becoming healthy with regular over-the-counter medicines and proper rest and care, for the severe patients, in the absence of definite cure, different drug combinations are being used to treat on trial basis without the assurance of efficacy and safety. This scenario has however changed now with some medicines including antiviral Remdesivir and Favipiravir and anti-inflammatory drugs like dexamethasone and tocilizumab which have shown some positive results in trials such as decreasing need of mechanical or non-invasive ventilation or mortality. Further, a number of vaccine candidates are currently in pipeline and in advance stages of clinical trials, which will enhance their prospects in determining how the disease will be controlled in the times to come. In this article, an account of the under-trial potential drugs and vaccine candidates has been provided, and their future prospects have been discussed.
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Project description:The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they are not specific and targeted. Therefore, several drugs have been investigated for their efficacy and safety in the treatment of COVID-19; most of them are undergoing clinical trials. This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial.
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Project description:Efficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARS-CoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis. We screened several clinical trials repositories and platforms in search of the prophylactic strategies being investigated against COVID-19 in July 2020. Up to July 5, 2020, only one clinical trial result was published, although we found 112 clinical trial protocols targeting medical workers (n=70, 63%), patients relatives (n=20, 18%) or individuals at risk of severe COVID-19 (n=14, 13%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n=69, 62%), before BCG vaccine (n=12, 11%), this followed by numerous antivirals and immune enhancers. Ninety-eight (88%) clinical trials were randomized with a median of planned inclusions of 530 (IQR 258-1299). Both pre- and post-exposure prophylaxes are investigated.
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Project description:Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first reported in December 2019 in Wuhan, China, but now more than 200 countries have been affected and the coronavirus pandemic is still ongoing. The severity of COVID-19 symptoms can range from mild to severe. FDA approved remdesivir as a treatment of COVID-19 so far. Various clinical trials are underway to find an effective method to treat patients with COVID-19. This review aimed at summarizing 219 registered clinical trials in the ClinicalTrials.gov database with possible mechanisms, and novel findings of them, and other recent publications related to COVID-19. According to our analyses, various treatment approaches and drugs are being investigated to find an effective drug to cure COVID-19 and among all strategies, three important mechanisms are suggested to be important against COVID-19 including antiviral, anti-inflammatory, and immunomodulatory properties. Our review can help future studies get on the way to finding an effective drug for COVID-19 treatment by providing ideas for similar researches.
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Project description:Coronavirus disease (COVID)-19 is the leading global health threat to date caused by a severe acute respiratory syndrome coronavirus (SARS-CoV-2). Recent clinical trials reported that the use of Bruton's tyrosine kinase (BTK) inhibitors to treat COVID-19 patients could reduce dyspnea and hypoxia, thromboinflammation, hypercoagulability and improve oxygenation. However, the mechanism of action remains unclear. Thus, this study employs structure-based virtual screening (SBVS) to repurpose BTK inhibitors acalabrutinib, dasatinib, evobrutinib, fostamatinib, ibrutinib, inositol 1,3,4,5-tetrakisphosphate, spebrutinib, XL418 and zanubrutinib against SARS-CoV-2. Molecular docking is conducted with BTK inhibitors against structural and nonstructural proteins of SARS-CoV-2 and host targets (ACE2, TMPRSS2 and BTK). Molecular mechanics-generalized Born surface area (MM/GBSA) calculations and molecular dynamics (MD) simulations are then carried out on the selected complexes with high binding energy. Ibrutinib and zanubrutinib are found to be the most potent of the drugs screened based on the results of computational studies. Results further show that ibrutinib and zanubrutinib could exploit different mechanisms at the viral entry and replication stage and could be repurposed as potential inhibitors of SARS-CoV-2 pathogenesis.
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